High hexacosanoic acid levels are associated with coronary artery disease

Miyazaki, Tatsuya; Shimada, Kazunori; Hiki, Makoto; Kume, Atsumi; Kitamura, Yohei; Oshida, Kyoichi; Yanagisawa, Naotake; Kobayashi, Takashi; Matsumori, Rie; Daida, Hiroyuki

doi:10.1016/j.atherosclerosis.2014.01.031

Cited by 17 publications

(10 citation statements)

References 29 publications

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“…Both of the products are governed by a rate limiting desaturase enzyme, SCD1. The conversion step of palmitic acid to palmitoleic acid that is dependent on SCD1 activity mainly occurs in hepatocytes and thus has been previously shown to play a major role in body weight, hepatic steatosis and obesity regulation 22 23. Our study adds to this literature by demonstrating a potential role of SCD1 in development of type 2 diabetes, independent of these factors.…”

Section: Discussionsupporting

confidence: 51%

Risk of diabetes associated with fatty acids in the de novo lipogenesis pathway is independent of insulin sensitivity and response: the Insulin Resistance Atherosclerosis Study (IRAS)

Qureshi

Santaren

Hanley

et al. 2019

BMJ Open Diab Res Care

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ObjectiveTo examine the associations of fatty acids in the de novo lipogenesis (DNL) pathway, specifically myristic acid (14:0), palmitic acid (16:0),cis-palmitoleic acid (c16:1 n-7),cis-myristoleic acid (c14:1n5), stearic acid (18:0) andcis-oleic acid (c18:1 n-9), with 5-year risk of type 2 diabetes. We hypothesized that DNL fatty acids are associated with risk of type 2 diabetes independent of insulin sensitivity.Research design and methodsWe evaluated 719 (mean age 55.1±8.5 years, 44.2% men, 42.3% Caucasians) participants from the Insulin Resistance Atherosclerosis Study. Multivariable logistic regression models with and without adjustment of insulin sensitivity were used to assess prospective associations of DNL fatty acids with incident type 2 diabetes.ResultsType 2 diabetes incidence was 20.3% over 5 years. In multivariable regression models, palmitic, palmitoleic, myristic, myristoleic and oleic acids were associated with increased risk of type 2 diabetes (p<0.05). Palmitic acid had the strongest association (OR per standard unit of palmitic acid 1.46; 95% CI 1.23 to 1.76; p<0.001), which remained similar with addition of insulin sensitivity and acute insulin response (AIR) to the model (OR 1.36; 95% CI 1.09 to 1.70, p=0.01). Oleic and palmitoleic acids were also independently associated with incident type 2 diabetes. In multivariable models, ratios of fatty acids corresponding to stearoyl CoA desaturase-1 and Elovl6 enzymatic activity were significantly associated with risk of type 2 diabetes independent of insulin sensitivity and AIR.ConclusionsWe observed associations of DNL fatty acids with type 2 diabetes incidence independent of insulin sensitivity.

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Section: Discussionsupporting

confidence: 51%

Risk of diabetes associated with fatty acids in the de novo lipogenesis pathway is independent of insulin sensitivity and response: the Insulin Resistance Atherosclerosis Study (IRAS)

Qureshi

Santaren

Hanley

et al. 2019

BMJ Open Diab Res Care

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“…10 However, in two other cross-sectional studies, VLCSFAs levels in serum or whole blood were positively associated with coronary artery disease prevalence or insulin resistance. 19, 20 Evidence regarding erythrocyte VLCSFAs is sparse and exclusively from cross-sectional studies. Interestingly, in these studies erythrocyte C24:0 or C26:0 were consistently correlated with atherogenic lipoprotein profiles or diabetes status.…”

Section: Discussionmentioning

confidence: 99%

Circulating Very-Long-Chain Saturated Fatty Acids and Incident Coronary Heart Disease in US Men and Women

et al. 2015

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Background Circulating very-long chain saturated fatty acids (VLCSFAs) may play an active role in the etiology of cardiometabolic diseases. Methods and Results We measured three VLCSFAs (C20:0, C22:0, and C24:0) in plasma and erythrocytes using gas-liquid chromatography among 794 incident coronary heart disease (CHD) cases who were prospectively identified and confirmed among women in Nurses' Health Study (NHS; 1990–2006) and among men in Health Professionals Follow-up Study (HPFS; 1994–2008). A total of 1233 CHD-free controls were randomly selected and matched to cases in these two cohorts. Conditional logistic regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). Plasma VLCSFAs were correlated with favorable profiles of blood lipids, C-reactive protein, and adiponectin in the NHS and HPFS, as well as with fasting insulin and C-peptide levels in a nationally-representative U.S. comparison population. After multivariate adjustment for lifestyle factors, body mass index (BMI), diet, and long-chain n-3 and trans fatty acids, total VLCSFAs in plasma was associated with a 52% decreased risk of CHD [pooled HR (95% CI); 0.48 (0.32, 0.72), comparing extreme quintiles; Ptrend<0.0001]. For VLCSFAs in erythrocytes, a non-significant inverse trend with CHD risk was observed [pooled HR (95% CI); 0.66 (0.41, 1.06), comparing extreme quintiles; Ptrend=0.16]. Conclusions In U.S. men and women, plasma VLCSFAs were independently associated with favorable profiles of blood lipids and other CVD risk markers and a lower risk of CHD. Erythrocyte VLCSFAs were associated with non-significant trends of lower CHD risk. Future studies are warranted to elucidate underlying biological mechanisms.

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“…The only remarkable result was the positive association of the NEFA 26:1, 26:2, and 26:6 levels at 5.5 years with the HOMA levels 2.5 years later. While very long-chain FA (VLCFA) with 20, 22 or 24 carbon atoms have been found to be related to lower diabetes risk and other beneficial effects on metabolic outcomes 61 , VLCFA with 26 carbon atoms were found to have positive associations with coronary artery disease and metabolic syndrome 62 . However, the biological role of these NEFA species is poorly investigated and further analyses replicating our findings in insulin-resistant patients would be important.…”

Section: Discussionmentioning

confidence: 99%

An individual participant data meta-analysis on metabolomics profiles for obesity and insulin resistance in European children

Hellmuth

Kirchberg

Brandt

et al. 2019

Sci Rep

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Childhood obesity prevalence is rising in countries worldwide. A variety of etiologic factors contribute to childhood obesity but little is known about underlying biochemical mechanisms. We performed an individual participant meta-analysis including 1,020 pre-pubertal children from three European studies and investigated the associations of 285 metabolites measured by LC/MS-MS with BMI z-score, height, weight, HOMA, and lipoprotein concentrations. Seventeen metabolites were significantly associated with BMI z-score. Sphingomyelin (SM) 32:2 showed the strongest association with BMI z-score (P = 4.68 × 10−23) and was also closely related to weight, and less strongly to height and LDL, but not to HOMA. Mass spectrometric analyses identified SM 32:2 as myristic acid containing SM d18:2/14:0. Thirty-five metabolites were significantly associated to HOMA index. Alanine showed the strongest positive association with HOMA (P = 9.77 × 10−16), while acylcarnitines and non-esterified fatty acids were negatively associated with HOMA. SM d18:2/14:0 is a powerful marker for molecular changes in childhood obesity. Tracing back the origin of SM 32:2 to dietary source in combination with genetic predisposition will path the way for early intervention programs. Metabolic profiling might facilitate risk prediction and personalized interventions in overweight children.

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High hexacosanoic acid levels are associated with coronary artery disease

Cited by 17 publications

References 29 publications

Risk of diabetes associated with fatty acids in the de novo lipogenesis pathway is independent of insulin sensitivity and response: the Insulin Resistance Atherosclerosis Study (IRAS)

Risk of diabetes associated with fatty acids in the de novo lipogenesis pathway is independent of insulin sensitivity and response: the Insulin Resistance Atherosclerosis Study (IRAS)

Circulating Very-Long-Chain Saturated Fatty Acids and Incident Coronary Heart Disease in US Men and Women

An individual participant data meta-analysis on metabolomics profiles for obesity and insulin resistance in European children

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